Acne vulgaris and other types of acne and acneiform skin maladies associated with hyperplasia of the sebaceous follicle are often treated by the oral administration of antibiotics. While oral administration of these drugs often constitutes an effective treatment regimen for acne, oral therapy has several disadvantages. For example, oral administration subjects the entire body to the antibiotic composition while only the localized acne lesion actually requires treatment. Moreover, almost all antibiotics have some undesirable side effects when taken orally. In contrast with oral dosing in the treatment of acne, topical application of antibiotics delivers the antibiotic to the afflicted situs and minimizes the antibiotic levels in the circulatory and gastrointestinal systems. Properly administered, the therapeutic benefit of topical antibiotic therapy in treating skin disorders can be comparable with, or superior to, that achieved by oral antibiotic therapy, while avoiding the undesirable side effects of oral administration.
The antibiotic erythromycin has frequently been proposed for topical use in the treatment of acne. However, erythromycin is known to have relatively poor storage stability when formulated in topical vehicles, making the formulation of such topical products difficult. Even more preferred for the topical treatment of acne, in terms of increased efficacy, is zinc erythromycin. However, the formulation of topical products containing zinc erythromycin presents an even greater storage stability problem since the presence of zinc in the composition acts to catalyze the erythromycin decomposition reaction. In the past, it has been proposed that this stability problem be handled by marketing zinc erythromycin products as separate pharmaceutical active and topical vehicle components which are mixed together into a single composition by the pharmacist immediately prior to dispensing to the patient. Such a technique for maximizing the shelf stability of topical zinc erythromycin compositions is, at best, cumbersome, and leads to the possibility of variations in the level of active component, as the composition is formulated by the pharmacist. It, therefore, would be highly desirable to be able to formulate a single phase dosage form in which the zinc erythromycin component exhibits extended shelf life stability.
U.S. Pat. No. 4,261,982, Luedders and Willins, issued Apr. 14, 1981, describes pharmaceutical compositions, especially useful in the topical treatment of acne, containing mixtures of zinc salts with erythromycin (zinc erythromycin). It is taught that these compositions may contain any of the common, non-water-based cosmetic topical carriers; a wide variety of such carriers is generically disclosed.
U.S. Pat. No. 3,562,806, Grant, et al, issued Feb. 9, 1971, describes a method and compositions for administration of pharmaceuticals to ruminants so as to avoid decomposition and deactivation of the pharmaceuticals. The pharmaceuticals are coated with the reaction product of an organic nitrogen-containing base, such as ethanolamine or diethanolamine, and an unsaturated cellulose derivative; the preferred coating material is cellulose propionate 3-morpholinobutyrate.
Belgian Pat. No. 889,327, Rorer International (Overseas) Inc., published Oct. 16, 1981, describes compositions for the topical treatment of acne containing an organic acyl peroxide together with an erythromycin compound. Some of the exemplified compositions include low levels of diisopropanolamine. These formulations are packed as separate carrier and erythromycin active components, with the two components being mixed together just prior to use.
U.S. Pat. No. 3,472,931, Stoughton, issued Oct. 14, 1969, describes compositions for enhancing the skin penetration of pharmaceutical actives, such as erythromycin, using lower alkyl amides, such as N,N-dimethyl acetamide or N,N-diethyl acetamide.
U.S. Pat. No. 4,000,263, Hebborn, issued Dec. 28, 1976, recognizes that erythromycin base exhibits poor stability in solution and provides topical compositions yielding improved stability of the erythromycin over prolonged periods of time. These compositions comprise erythromycin base, propylene glycol, ethanol, and an ethoxylated ether of lauryl alcohol.
U.S. Pat. No. 3,927,197, Monkhouse, issued Dec. 16, 1975, describes pharmaceutical compositions containing E-series prostaglandins together with saturated tertiary aliphatic alcohols having 4 to 10 carbon atoms, such as t-butanol, as a stabilizing component.
U.S. Pat. No. 4,006,218, Sipos, issued Feb. 1, 1977, describes antimicrobial compositions, having enhanced activity, containing an antimicrobial agent, such as erythromycin, together with a potentiator, such as a primary, secondary or tertiary monohydric alcohol having a straight chain of from 5 to 10 carbon atoms.
French Pat. No. 2,383,667, Desjonqueres, published Oct. 13, 1978, describes compositions for the topical treatment of acne comprising erythromycin base or salts together with a hydrating excipient, such as chloroform.
Chemical Abstracts 55:13767 describes a study indicating that barbiturates in aqueous solution may be stabilized by lowering the dielectric constant of the solution. In the experiments, the dielectric constant of various solutions tested was lowered by the addition of methanol, ethanol, polyalcohols or sugars.
By the present invention, novel zinc erythromycin compositions characterized by enhanced storage stability properties are provided. The compositions can be formulated as a single package product without any significant risk of decomposition of the zinc erythromycin active over the typical product shelf life (for example, one to three years). The compositions herein are suitable for human and veterinary uses. They exhibit antifungal activity and are especially useful when applied topically in the treatment of acne.